Variant 5-35644519-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024867.4(SPEF2):c.579T>C(p.Ile193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 1,591,038 control chromosomes in the GnomAD database, including 356,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 37557 hom., cov: 32)

Exomes 𝑓: 0.66 ( 318968 hom. )

Consequence

SPEF2
NM_024867.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.13

Variant links:

Genes affected

SPEF2 (HGNC:26293): (sperm flagellar 2) Involved in sperm axoneme assembly. Located in sperm flagellum. Implicated in spermatogenic failure 43. [provided by Alliance of Genome Resources, Apr 2022]

SPEF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 5-35644519-T-C is Benign according to our data. Variant chr5-35644519-T-C is described in ClinVar as [Benign]. Clinvar id is 403472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPEF2	NM_024867.4 linkuse as main transcript	c.579T>C	p.Ile193=	synonymous_variant	4/37	ENST00000356031.8	NP_079143.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPEF2	ENST00000356031.8 linkuse as main transcript	c.579T>C	p.Ile193=	synonymous_variant	4/37	1	NM_024867.4	ENSP00000348314	P2	Q9C093-1

Frequencies

GnomAD3 genomes

AF:

0.698

AC:

106056

AN:

151918

Hom.:

37496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.774

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.725

Gnomad ASJ

AF:

0.660

Gnomad EAS

AF:

0.869

Gnomad SAS

AF:

0.826

Gnomad FIN

AF:

0.609

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.643

Gnomad OTH

AF:

0.674

GnomAD3 exomes

AF:

0.707

AC:

162203

AN:

229368

Hom.:

58134

AF XY:

0.703

AC XY:

87402

AN XY:

124254

show subpopulations

Gnomad AFR exome

AF:

0.779

Gnomad AMR exome

AF:

0.794

Gnomad ASJ exome

AF:

0.663

Gnomad EAS exome

AF:

0.866

Gnomad SAS exome

AF:

0.815

Gnomad FIN exome

AF:

0.628

Gnomad NFE exome

AF:

0.641

Gnomad OTH exome

AF:

0.680

GnomAD4 exome

AF:

0.663

AC:

953405

AN:

1439002

Hom.:

318968

Cov.:

AF XY:

0.666

AC XY:

476156

AN XY:

715286

show subpopulations

Gnomad4 AFR exome

AF:

0.779

Gnomad4 AMR exome

AF:

0.781

Gnomad4 ASJ exome

AF:

0.659

Gnomad4 EAS exome

AF:

0.875

Gnomad4 SAS exome

AF:

0.810

Gnomad4 FIN exome

AF:

0.633

Gnomad4 NFE exome

AF:

0.637

Gnomad4 OTH exome

AF:

0.678

GnomAD4 genome

AF:

0.698

AC:

106183

AN:

152036

Hom.:

37557

Cov.:

AF XY:

0.699

AC XY:

51961

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.775

Gnomad4 AMR

AF:

0.725

Gnomad4 ASJ

AF:

0.660

Gnomad4 EAS

AF:

0.868

Gnomad4 SAS

AF:

0.826

Gnomad4 FIN

AF:

0.609

Gnomad4 NFE

AF:

0.643

Gnomad4 OTH

AF:

0.677

Alfa

AF:

0.652

Hom.:

52204

Bravo

AF:

0.707

Asia WGS

AF:

0.830

AC:

2886

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Spermatogenic failure 43

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.36

DANN

Benign

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over